Structural Superimposition

Abstact

Brassinosteroids (BRs) are chemically diverse plant steroid hormones produced via a branched biosynthetic pathway. The potent BR brassinolide is sensed by the membrane receptor kinase BRI1 and a SERK co-receptor, but the physiological functions of other abundant BRs remain to be characterized. Here we present quantitative binding kinetics for 4 Arabidopsis thaliana BR receptors and 15 BRs, which define the key chemical features required for high-affinity receptor binding, ligand positioning and co-receptor recognition. BRI1, BRL1 and BRL3 share overlapping ligand preferences, whereas BRL2 binds C(28) BRs with moderate affinity. Structural analyses of BR-bound BRI1 and BRL3 ectodomains combined with extensive in vitro and in vivo mutagenesis studies reveal a high structural plasticity of the hormone-binding pocket. Functional assays using structure-based BR agonists and antagonists uncover that BR receptor-co-receptor signalling complexes can recognize chemically diverse BRs, introducing an additional, intriguing layer of BR signalling regulation.